Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells

Jeon, Yu Jin; Kim, Joong Sun; Hwang, Geun Hye; Wu, Zhexue; Han, Ho Jae; Park, Soo Hyun; Chang, Won Hyuk; Kim, Lark Kyun; Lee, You‐Mie; Liu, Kwang-Hyeon; Lee, Min Young

doi:10.1016/j.ejphar.2015.07.047

Cited by 43 publications

(19 citation statements)

References 33 publications

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“…In this respect, Tanshinone IIA (TAN) is one of the most extensively studied. As the major functional compound of Danshen, TAN has been shown to antagonize the proliferation of multiple human cancer cell lines, such as human hepatocellular carcinoma cells, human non–small cell lung cancer, and human promyelocytic leukemia cell . Moreover, Ding et al.…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA induces cell death via Beclin‐1‐dependent autophagy in oral squamous cell carcinoma SCC‐9 cell line

Qiu

Wang

et al. 2018

Cancer Medicine

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Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis‐ and autophagy‐inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC‐9 was used for in vitro assays and induction in an OSCC xenograft mouse model. The tumor cells were subjected to TAN administration at different concentrations. Then the apoptosis and autophagy processes in SCC‐9 cells were evaluated and the activities of Beclin‐1/Atg7/Atg12‐Atg5 and PI3K/Akt/mTOR pathways were determined. In addition, by knocking down the expression of Beclin‐1 in SCC‐9 cells, the study also assessed the role of the indicator in the anti‐OSCC effect of TAN. Results of in vitro assays were further validated with an OSCC xenograft mouse model. Administration of TAN‐induced cell apoptosis and upregulated the expression of cleaved‐caspase‐3. Simultaneously, the autophagy process in SCC‐9 cells was initiated by TAN, which was signaled by the formation of autophagosomes and increase in the ratio of LC3 II/LC3I. The above processes were associated with the activation of Beclin‐1/Atg7/Atg12‐Atg5 signaling and inhibition of PI3K/Akt/mTOR signaling. Our results also inferred a partially Beclin‐1‐dependent mechanism of action of TAN in OSCC cells: knockdown of the Beclin‐1 blocked the effect of TAN on SCC‐9 cells both in vivo and in vitro. Our study provided a preliminary explanation of the mechanism involved in TAN effect: the agent exerted its autophagy‐inducing effect against OSCC in a multipronged manner, by both inducing the Beclin‐1/Atg7/Atg12‐Atg5 pathway and suppressing the PI3K/Akt/mTOR pathway.

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Section: Introductionmentioning

confidence: 99%

Tanshinone IIA induces cell death via Beclin‐1‐dependent autophagy in oral squamous cell carcinoma SCC‐9 cell line

Qiu

Wang

et al. 2018

Cancer Medicine

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“…Tanshinone IIA shows a variety of biological activities, including antibacterial, antiphlogistic, and antioxidative activities (Shu, Hu, Hung, Huang, & Zhang, ; Zeng et al, ). Moreover, Tanshinone IIA was also reported with antitumor activities in many kinds of carcinomas (Jeon et al, ; Jing et al, ; Lin et al, ; Yu, Xue, Zhou, Li, & Zhou, ; Yun et al, ). The antibreast cancer ability of tanshinone is related to its antiestrogenic properties (Zhao et al, ), which is one of the main targets of estrogen positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Tanshinone IIA combined with Taxol on drug‐resist breast cancer cells MCF‐7 through inhibition of Tau

Lin

Zheng

Xie

et al. 2018

Phytotherapy Research

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Drug resistance represents a major obstacle to improving the overall response and survival of cancer patients. Taxol is one of the most commonly used chemotherapy agents in breast cancer. As with many cancer therapeutic agents, resistance remains a significant problem when using Taxol to treat malignancies. In this study, estrogen receptor positive breast cancer cells MCF-7 were induced Taxol resistance. And Tanshinone IIA combined with Taxol was chosen to treat it. The drugs combination showed additive effect in most drug concentrations. Drug resistance cancer cells showed a higher microtubule associated protein (Tau) expression, which was considered as one of the reasons for Taxol resistance. Tanshinone IIA inhibited the expression of Tau in MCF-7 cells and resulted in higher sensibility of Taxol. Moreover, Tanshinone IIA also showed cytotoxicity to MCF-7, which might be related to its estrogenicity effect. In conclusion, the combination of Tanshinone IIA and Taxol showed higher cytotoxicity to Taxol resistant MCF-7 cells, which might be related to the inhibition of Tau.

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“…Overexpression of CYP2J2 has been implicated in the pathogenesis of human cancers and resistance to chemotherapy and is believed to be a potential target to reduce cancer cell proliferation and resistance to chemotherapy. [216][217][218] For example, tanshinone IIA dosedependently and noncompetitively inhibits CYP2J2-mediated astemizole O-demethylation activity, and it significantly decreased viability of human hepatoma HepG2 cells and SiHa cervical cancer cells. 217 Tanshinone IIA-induced apoptotic cell death rate was also significantly attenuated by enhanced upregulation of CYP2J2 expression.…”

Section: Potential Use In Oncologymentioning

confidence: 99%

“…[216][217][218] For example, tanshinone IIA dosedependently and noncompetitively inhibits CYP2J2-mediated astemizole O-demethylation activity, and it significantly decreased viability of human hepatoma HepG2 cells and SiHa cervical cancer cells. 217 Tanshinone IIA-induced apoptotic cell death rate was also significantly attenuated by enhanced upregulation of CYP2J2 expression. CYP2J2 is inhibited by astemizole and loratadine (as well as cisapride).…”

Section: Potential Use In Oncologymentioning

confidence: 99%

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

Shah

Stonier

2018

J Clin Pharm Ther

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Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death in hepatocellular carcinoma HepG2 cells

Cited by 43 publications

References 33 publications

Tanshinone IIA induces cell death via Beclin‐1‐dependent autophagy in oral squamous cell carcinoma SCC‐9 cell line

Tanshinone IIA induces cell death via Beclin‐1‐dependent autophagy in oral squamous cell carcinoma SCC‐9 cell line

Cytotoxicity of Tanshinone IIA combined with Taxol on drug‐resist breast cancer cells MCF‐7 through inhibition of Tau

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

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